Near infrared (NIR)-emitting persistent luminescent nanoparticles have been developed as potential agents for bioimaging. However, synthesizing uniform nanoparticles with long afterglow for long-term imaging is lacking. Here, we demonstrated the synthesis of spinel structured Zn3Ga2Ge2O10:Cr3+ (ZGGO:Cr3+) and Zn3Ga2Ge2O10:Cr3+,Eu3+ (ZGGO:Cr3+,Eu3+) nanoparticles by a sol-gel method in combination with a subsequent reducing atmosphere-free calcination. The samples were investigated via detailed characterizations by combined techniques of XRD, TEM, STEM, selected area electron diffraction, photoluminescence excitation (PLE)/photoluminescence (PL) spectroscopy, and temperature-dependent PL analysis. The single-crystalline nanoparticles are homogeneous solid solution, possessing uniform cubic shape and lateral size of ~ 80–100 nm. Upon UV excitation at 273 nm, ZGGO:Cr3+,Eu3+ exhibited a NIR emission band at 697 nm (2E → 4A2 transition of distorted Cr3+ ions in gallogermanate), in the absence of Eu3+ emission. NIR persistent luminescence of the sample can last longer than 7200 s and still hold intense intensity. Eu3+ incorporation increased the persistent luminescence intensity and the afterglow time of ZGGO:Cr3+, but it did not significantly affect the thermal stability. The obtained ZGGO:Cr3+,Eu3+-NH2 nanoparticles possessed an excellent imaging capacity for cells in vitro.